A betacellulin protein (hereinafter also referred to as BTC protein) is a peptide factor produced by pancreatic beta tumor cells derived from a transgenic mouse, and its full amino acid sequence has been clarified by cDNA analysis [Shing et al., Science, 259:1604 (1993); Sasada et al., Biochemical and Biophysical Research Communications, 190:1173 (1993)]. Although BTC protein was first discovered as a factor possessing mouse 3T3 cell growth-promoting activity, it was later found to exhibit growth-promoting activity against vascular smooth muscle cells and retinal pigment epithelial cells [Shing et al., Science, 259:1604 (1993)].
A human BTC protein naturally occurs in very trace amounts, and attempts to obtain it from human tissue has been very difficult by various limitations. In recent years, however, gene engineering techniques have been successfully used to produce highly purified human BTC protein in large amounts and at relatively low costs (EP-A-0555785). Also, it has been reported that BTC protein can be used in the treatment of diseases such as wounds, tumors and vascular malformations, and preparation of competitive agents such as an antibodies or false peptides which can be used in the treatment of such diseases attributable to smooth muscle growth as atherosclerosis and diabetic retinopathy (EP-A-0482623, EP-A-0555785).
In addition, the mRNA of BTC protein has been detected in non-brain organs, e.g., liver, kidney and pancreas, suggesting that BTC protein exhibits some function in these organs as well, but much remains to be known in detail.